Chiam K-H, Rajagopal Gunaretnam
Institute of High Performance Computing, 1 Science Park Road, Singapore 117528, Singapore.
Phys Rev E Stat Nonlin Soft Matter Phys. 2007 Jun;75(6 Pt 1):061901. doi: 10.1103/PhysRevE.75.061901. Epub 2007 Jun 1.
In this paper, we study the oscillatory dynamics of intracellular signaling cascades. We derive a reaction-diffusion model of the mitogen-activated protein kinase cascade, and use it to show how oscillations of the protein kinase concentrations can occur as a function of the depth of the cascade. We find that only cascades with depths of three or more layers undergo oscillatory instabilities. In addition, the oscillatory instability is spatially uniform. Thus, the oscillations synchronize the protein kinase concentrations and result in them being uniformly distributed in the cytosol, despite the presence of protein kinase diffusion. Finally, we show how the oscillations are perturbed when parallel cascades "crosstalk." We find that the protein kinases in the downstream layers of the cascade are less perturbed than those in the upstream layers. In particular, cascades of three layers are able to maintain the total power of the protein kinase activities at approximately the unperturbed level. Taken together, our results suggest that only cascades of at least three layers can synchronize the oscillations of protein kinases in the cytosol and operate in parallel in the presence of crosstalk without loss of signaling fidelity.
在本文中，我们研究细胞内信号级联的振荡动力学。我们推导了丝裂原活化蛋白激酶级联的反应扩散模型，并用它来展示蛋白激酶浓度的振荡如何作为级联深度的函数而发生。我们发现只有深度为三层或更多层的级联会经历振荡不稳定性。此外，振荡不稳定性在空间上是均匀的。因此，振荡使蛋白激酶浓度同步，并导致它们在胞质溶胶中均匀分布，尽管存在蛋白激酶扩散。最后，我们展示了平行级联“串扰”时振荡是如何受到扰动的。我们发现级联下游层中的蛋白激酶比上游层中的蛋白激酶受到的扰动更小。特别是，三层级联能够将蛋白激酶活性的总功率维持在大约未受扰动的水平。综上所述，我们的结果表明，只有至少三层的级联才能使胞质溶胶中蛋白激酶的振荡同步，并在存在串扰的情况下并行运作而不损失信号保真度。
